Role of preoperative circulating tumor DNA in predicting occult metastases in resectable and borderline resectable pancreatic ductal adenocarcinoma

doi:10.3748/wjg.v31.i32.109383

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World Journal of Gastroenterology

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1007-9327

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World J Gastroenterol. Aug 28, 2025; 31(32): 109383
Published online Aug 28, 2025. doi: 10.3748/wjg.v31.i32.109383

Role of preoperative circulating tumor DNA in predicting occult metastases in resectable and borderline resectable pancreatic ductal adenocarcinoma

Takeshi Murakami, Masafumi Imamura, Yasutoshi Kimura, Kazunori Watanabe, Yoshihito Shinohara, Toru Nakamura, Siew-Kee Low, Masayo Motoya, Yujiro Kawakami, Yoshiharu Masaki, Tomohiro Kubo, Makoto Yoshida, Eiji Yoshida, Toru Kato, Kazuharu Kukita, Daisuke Kyuno, Ichiro Takemasa

Takeshi Murakami, Masafumi Imamura, Yasutoshi Kimura, Eiji Yoshida, Toru Kato, Kazuharu Kukita, Daisuke Kyuno, Ichiro Takemasa, Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, Sapporo 060-0061, Hokkaidō, Japan

Kazunori Watanabe, Yoshihito Shinohara, Toru Nakamura, Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, Sapporo 060-0808, Hokkaidō, Japan

Kazunori Watanabe, Yoshihito Shinohara, Siew-Kee Low, Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Ariake 135-8550, Tokyo, Japan

Masayo Motoya, Center for Gastroenterology, Teine Keijinkai Hospital, Sapporo 006-0811, Hokkaidō, Japan

Yujiro Kawakami, Yoshiharu Masaki, Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo 060-0061, Hokkaidō, Japan

Tomohiro Kubo, Makoto Yoshida, Department of Medical Oncology, Sapporo Medical University School of Medicine, Sapporo 060-0061, Hokkaidō, Japan

Author contributions: Murakami T, Imamura M, Kimura Y, and Nakamura T designed the study; Murakami T, Imamura M, Kawakami Y, Nakamura T, Motoya M, Masaki Y, Kubo T, Yoshida M, Yoshida E, Kato T, and Kukita K collected and assessed clinical data; Watanabe K, Shinohara Y, and Low SK performed circulating tumor DNA analysis; Murakami T wrote the first draft of the manuscript; Imamura M, Kimura Y, and Kyuno D revised the manuscript; Kimura Y and Takemasa I supervised the study; All authors reviewed the results and approved the final version of the manuscript.

Supported by the Council for Science, Technology, and Innovation (CSTI) Cross-Ministerial Strategic Innovation Promotion Program (SIP) “Innovative AI Hospital System” (National Institute of Biomedical Innovation, Health and Nutrition), No. SIPAIH18C03; and the Japan Society for the Promotion of Science (JSPS) KAKENHI, No. JP19K09179 and No. JP23K08158.

Institutional review board statement: This study was approved by the Institutional Review Board of Sapporo Medical University (No. 302-240), Hokkaido University (No. 18-053), and the Japanese Foundation for Cancer Research (No. 2018-1016 and No. 2020-1150).

Clinical trial registration statement: This study was registered in the University Hospital Medical Information Network Clinical Trials Registry (registration No. UMIN 000054546). Details are available at https://center6.umin.ac.jp/cgi-bin/ctr/ctr_view_reg.cgi?recptno=R000062319.

Informed consent statement: All eligible patients provided written informed consent before participation.

Conflict-of-interest statement: The authors declare that they have no conflict of interest.

CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.

Data sharing statement: The data generated in this study are available upon request from the corresponding author.

Corresponding author: Masafumi Imamura, MD, PhD, Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo 060-0061, Hokkaidō, Japan. imamura@sapmed.ac.jp

Received: May 9, 2025
Revised: June 6, 2025
Accepted: August 1, 2025
Published online: August 28, 2025
Processing time: 110 Days and 16.1 Hours

Abstract

BACKGROUND

Some patients with resectable or borderline resectable pancreatic ductal adenocarcinoma (PDAC) may have distant metastases, undetected on preoperative imaging or early recurrence, within 6 months after surgery. Occult metastases (OMs) must be accurately predicted to optimize multidisciplinary treatment.

AIM

To investigate the efficacy of circulating tumor DNA (ctDNA) in predicting OM.

METHODS

Two Japanese institutions prospectively collected preoperative plasma samples from PDAC patients between July 2019 and September 2021 and evaluated ctDNA using a targeted next-generation sequencing panel covering 52 cancer-related genes.

RESULTS

Among 135 PDAC patients, 38 had OM and 35 were positive for ctDNA. The ctDNA positivity rate was significantly higher in patients with OM than in patients without OM. ctDNA-positive patients had significantly shorter median recurrence-free survival than ctDNA-negative patients. Logistic multivariate regression revealed ctDNA positivity as an independent predictor of OM.

CONCLUSION

Preoperative ctDNA in resectable PDAC is an independent predictor of OM and indicates poor prognosis following pancreatectomy and may be a useful biomarker in determining multidisciplinary patient care.

Keywords: Pancreatic ductal adenocarcinoma; Occult metastases; Early recurrence; Multidisciplinary treatment; Circulating tumor DNA

Core Tip: Circulating tumor DNA (ctDNA) levels, when used alongside conventional biomarkers, may offer valuable insights for developing individualized treatment strategies in pancreatic ductal adenocarcinoma. These include determining the optimal regimen and duration of neoadjuvant therapy. In addition, ctDNA may help identify the most appropriate timing for surgery, thereby enabling more precise treatment decisions and potentially contributing to improved clinical outcomes and long-term prognosis.